Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
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Comparison of Optical Genome Mapping With Conventional Diagnostic Methods for Structural Variant Detection in Hematologic Malignancies

  • Yeeun Shim (Brain Korea 21 PLUS Project for Medical Science, Yonsei University) ;
  • Yu-Kyung Koo (Department of Laboratory Medicine, Yonsei University College of Medicine) ;
  • Saeam Shin (Department of Laboratory Medicine, Yonsei University College of Medicine) ;
  • Seung-Tae Lee (Department of Laboratory Medicine, Yonsei University College of Medicine) ;
  • Kyung-A Lee (Department of Laboratory Medicine, Yonsei University College of Medicine) ;
  • Jong Rak Choi (Department of Laboratory Medicine, Yonsei University College of Medicine)
  • Received : 2023.08.31
  • Accepted : 2024.02.13
  • Published : 2024.07.01
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Abstract

Background: Structural variants (SVs) are currently analyzed using a combination of conventional methods; however, this approach has limitations. Optical genome mapping (OGM), an emerging technology for detecting SVs using a single-molecule strategy, has the potential to replace conventional methods. We compared OGM with conventional diagnostic methods for detecting SVs in various hematologic malignancies. Methods: Residual bone marrow aspirates from 27 patients with hematologic malignancies in whom SVs were observed using conventional methods (chromosomal banding analysis, FISH, an RNA fusion panel, and reverse transcription PCR) were analyzed using OGM. The concordance between the OGM and conventional method results was evaluated. Results: OGM showed concordance in 63% (17/27) and partial concordance in 37% (10/27) of samples. OGM detected 76% (52/68) of the total SVs correctly (concordance rate for each type of SVs: aneuploidies, 83% [15/18]; balanced translocation, 80% [12/15] unbalanced translocation, 54% [7/13] deletions, 81% [13/16]; duplications, 100% [2/2] inversion 100% [1/1]; insertion, 100% [1/1]; marker chromosome, 0% [0/1]; isochromosome, 100% [1/1]). Sixteen discordant results were attributed to the involvement of centromeric/telomeric regions, detection sensitivity, and a low mapping rate and coverage. OGM identified additional SVs, including submicroscopic SVs and novel fusions, in five cases. Conclusions: OGM shows a high level of concordance with conventional diagnostic methods for the detection of SVs and can identify novel variants, suggesting its potential utility in enabling more comprehensive SV analysis in routine diagnostics of hematologic malignancies, although further studies and improvements are required.

Keywords

Acknowledgement

This work was supported by a grant from the National Research Foundation of Korea (NRF-2021R1I1A1A01045980).

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